Parkinson's disease is a relatively common neurological condition characterized by degeneration of neurons in the substantia nigra and a resulting dopamine dificiency in the caudate nucleus and putamen. When dopamine is replaced in brain by L-dopa therapy, symptoms of akinesian, tremor and rigidity are relieved. Despite the success of L-dopa therapy, little is known about the role of dopamine in the regulation of normal movement. We have recently discovered that rats which have been trained to turn in circles release dopamine predominantly from the side of caudate contralateral to their turning direction. The recent development of in vivo electrochemical electrodes has made it possible to study dopamine metabolism in awake, moving animals. Using this technique as well as traditional, direct tissue assays for dopamine and its metabolite DOPAC, we have shown that there is increased dopamine turnover in the caudate contralateral to the trained turning direction. We plan to further characterize the neurochemical changes associated with voluntary circling behavior by measuring the synthetic enzyme tyrosine hydroxylase and the synthesis rates of acetylcholine and serotonin on both sides of caudate before, during, and after circling. We will also look for changes in dopamine receptor number and affinity over the same time course. Other brain regions including substantia nigra, nucleus accumbens, amygdala, globus pallidus, and laternal septal nucleus will be recorded during turning behavior. The unilateral 6-hydroxydopamine substantia nigra lesion model will be combined with trained behavior to model volitional behavior and Parkinson's disease. Efforts will be made to restore normal trained behavior in this model by treatment with dopamine agonists. These experiments will imporve understanding of the anatomical and neurochemical relationships associated with normal and pathological movement.